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The Myxococcus xanthus Pho regulon: functional characterisation of a complex system with multiple regulatory components

Reference	BB/D003989/1
Principal Investigator / Supervisor	Professor David Hodgson
Co-Investigators / Co-Supervisors	Professor David Scanlan, Professor D E Whitworth
Institution	University of Warwick
Department	Biological Sciences
Funding type	Research
Value (£)	205,186
Status	Completed
Type	Research Grant
Start date	01/10/2005
End date	31/08/2009
Duration	47 months

Abstract

Phosphate acquisition is a fundamental challenge for all life forms. Myxobacteria appear to have met this challenge in a similar but essentially different way to the well-studied paradigms of Bacillus subtilis and Escherichia coli. Myxococcus xanthus is a social predator which is also capable of multicellular development, and as such it is expected to experience different requirements/opportunities for phosphate acquisition than other soil-dwelling organisms. Our preliminary data suggests that the Pho regulon of M. xanthus is unprecedented in its complexity and we wish to perform a thorough analysis of the physiology and molecular biology of the Pho system. To this end we will study three major aspects of the Pho regulon. Firstly, we will assess phosphate availability to the organism throughout its developmental cycle and identify phosphorus-containing molecules that can be used as phosphorus sources. Secondly, we will identify Pho genes that are involved in the uptake and metabolism of phosphorus. Pho gene function will be elucidated genetically and if possible biochemically using purified components. Thirdly, we will investigate the phosphate-dependent regulation of Pho gene expression. To achieve this we will characterise mutants of the regulatory genes for altered physiology, and assess the activity of regulator-dependent genes in various regulator mutant backgrounds. The biochemistry of promoter/recognition by the different regulators will be assessed in vitro and negative regulators of the Pho regulon will also be characterised. By systematically investigating the Pho regulon we will elucidate how phosphate acquisition is regulated during vegetative growth and during development. We will also assess the functional properties of the Myxococcus Pho regulon that are granted by the increase in regulatory complexity.

Summary

All forms of life have a nutritional need to acquire the element phosphorus. Phosphorus is required as a building block for the genetic material DNA and various membrane components, as well as being vitally important in cellular processes such as metabolism, and responding to changes in the environment. All organisms must acquire phosphorus, yet it is available to different organisms in different chemical forms. For instance as phosphate, it can be found as an inorganic ion which most organisms can take up directly from their surroundings. However, in some environments (for example in soil), phosphate is present in very low concentrations. Therefore organisms living in soil such as plants and bacteria, have to acquire their phosphorus from other sources. One such source of phosphorus is the DNA and cellular components found within other organisms, and a group of soil bacteria called the myxobacteria have evolved ways of acquiring phosphorus from this source. The myxobacteria have two modes of existence. In one form a population of myxobacteria swarms through the soil searching for prey organisms. When myxobacteria find prey they secrete digestive enzymes, which break open the cells of the prey. The myxobacteria then consume the materials released from the prey cells, including phosphorus-containing cellular components. When prey is scarce, myxobacteria will aggregate and co-operatively form a multicellular structure called a fruiting body. Within the fruiting body some myxobacteria burst open, presumably releasing nutrients that the surviving myxobacteria are thought to take up. In this way, the sacrifice of the few provides nutrients (including phosphorus) to the rest of the population of cells, enabling them to change into spores (heat and drought-resistant cell survival forms). Spores are able to survive for long periods, until prey or other forms of nutrients become available once again. At the current time we do not know how myxobacteria acquire phosphorus, orwhether they use different sources of phosphorus depending on whether they are feeding on prey, or cannibalising themselves during formation of a fruiting body. We do know that myxobacteria possess extremely sophisticated regulatory mechanisms for controlling how they acquire phosphorus, but how the regulatory mechanisms operate is unclear. In the proposed research programme, we wish to study every aspect of how myxobacteria acquire phosphorus. We wish to identify the phosphorus-containing compounds that are available to myxobacteria, both as they feed upon prey and as they form a fruiting body. When we know which compounds are available to the myxobacteria we will determine which of those phosphorus sources the myxobacteria can (and do) utilise. The next step of the research will be to identify the genes directly responsible for taking up phosphorus-containing compounds, and the genes that regulate phosphorus uptake. When we have identified the phosphorus-uptake genes, we will investigate the properties of those genes and their gene products. The ultimate goal of the project will be to gain a complete appreciation of phosphorus acquisition in the myxobacteria. We wish to understand how changes in gene expression lead to altered phosphorus-uptake by the bacteria in different physiological states and environments. One of the biggest challenges will be to understand how the complex regulatory system possessed by the myxobacteria enables it to acquire phosphorus in the unusual ways it does.

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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